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WO2008073365A1 - Inhibiteurs de la protéase d'aspartyle - Google Patents

Inhibiteurs de la protéase d'aspartyle Download PDF

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Publication number
WO2008073365A1
WO2008073365A1 PCT/US2007/025220 US2007025220W WO2008073365A1 WO 2008073365 A1 WO2008073365 A1 WO 2008073365A1 US 2007025220 W US2007025220 W US 2007025220W WO 2008073365 A1 WO2008073365 A1 WO 2008073365A1
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formula
another embodiment
group
alkyl
lll
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Inventor
Zhaoning Zhu
Andrew Stamford
Mihirbaran Mandal
Xiaoxiang Liu
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Merck Sharp and Dohme LLC
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Schering Corp
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Priority to MX2009006228A priority Critical patent/MX2009006228A/es
Priority to AU2007332754A priority patent/AU2007332754A1/en
Priority to CA002672293A priority patent/CA2672293A1/fr
Priority to JP2009541321A priority patent/JP2010512389A/ja
Priority to EP07862708.0A priority patent/EP2064191B1/fr
Priority to US12/517,744 priority patent/US8093254B2/en
Publication of WO2008073365A1 publication Critical patent/WO2008073365A1/fr
Anticipated expiration legal-status Critical
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4

Definitions

  • This invention relates to aspartyl protease inhibitors, pharmaceutical compositions comprising said compounds, their use in the treatment of cardiovascular diseases, cognitive and neurodegenerative diseases, and their use as inhibitors of the Human Immunodeficiency Virus, plasmepsins, cathepsin D and protozoal enzymes.
  • Angiotensin-ll a potent vasoconstrictor and stimulator for release of adrenal aldosterone, was processed from the precursor decapeptide Angiotensin-I, which in turn is processed from angiotensinogen by the renin enzyme.
  • Angiotensin-ll is also found to play roles in vascular smooth muscle cell growth, inflammation, reactive oxygen species generation and thrombosis and influence atherogenesis and vascular damage.
  • Clinically, the benefit of interruption of the generation of angiotensin-ll through antagonism of conversion of angiotensin-l has been well known and there are a number of ACE inhibitor drugs on the market.
  • renin is an aspartyl protease whose only natural substrate is angiotensinogen, it is believed that there would be less frequent adverse effect for controlling high blood pressure and related symptoms regulated by angiotensin-ll through its inhibition.
  • Another protease, Cathepsin-D is involved in lysosomal biogenesis and protein targeting, and may also be involved in antigen processing and presentation of peptide fragments. It has been linked to numerous diseases including, Alzheimer's, Disease, connective tissue disease, muscular dystrophy and breast cancer.
  • AD Alzheimer's Disease
  • a ⁇ extracellular ⁇ -amyloid
  • Amyloid plaques consist predominantly of A ⁇ peptides comprised of 40 - 42 amino acid residues, which are derived from processing of amyloid precursor protein (APP).
  • APP is processed by multiple distinct protease activities.
  • a ⁇ peptides result from the cleavage of APP by ⁇ -secretase at the position corresponding to the N-terminus of A ⁇ , and at the C- terminus by ⁇ -secretase activity.
  • APP is also cleaved by ⁇ -secretase activity resulting in the secreted, non-amyloidogenic fragment known as soluble APP.
  • BACE-1 An aspartyl protease known as BACE-1 has been identified as the ⁇ -secretase activity responsible for cleavage of APP at the position corresponding to the N- terminus of A ⁇ peptides.
  • BACE-1 An aspartyl protease known as BACE-1 has been identified as the ⁇ -secretase activity responsible for cleavage of APP at the position corresponding to the N- terminus of A ⁇ peptides.
  • a ⁇ has been shown to be toxic to neuronal cells in vitro and when injected into rodent brains.
  • inherited forms of early-onset AD are known in which well-defined mutations of APP or the presenilins are present. These mutations enhance the production of A ⁇ and are considered causative of AD.
  • inhibition of BACE-1 should inhibit formation of A ⁇ peptides.
  • inhibition of BACE-1 is a therapeutic approach to the treatment of AD and other cognitive and neurodegenerative diseases caused by or associated with A ⁇ plaque deposition.
  • Glaucoma a major cause of blindness worldwide, is an example of another neurodegenerative disease in which A ⁇ may play a causative role. Glaucoma is commonly linked to elevated intraocular pressure (lOP). It is well known that raised IOP can lead to irreversible destruction of retinal ganglion cells (RGCs). However, the presence of glaucomatous damage in patients with normalized IOP has focused a growing body of work on alternative strategies to those regulating IOP. Recent evidence suggests that targeting A ⁇ deposition associated with Alzheimers Disease may provide a therapeutic avenue in glaucoma treatment. For example, Guo et al.
  • HIV Human immunodeficiency virus
  • AIDS acquired immune deficiency syndrome
  • compounds such as indinavir, ritonavir and saquinavir which are inhibitors of the HIV aspartyl protease result in lowering of viral load.
  • the compounds described herein would be expected to be useful for the treatment of AIDS.
  • HIV-1 protease an aspartyl protease related to renin.
  • HTLV-I Human T-cell leukemia virus type I
  • HTLV-I Human T-cell leukemia virus type I
  • HTLV-I Like other retroviruses, HTLV-I requires an aspartyl protease to process viral precursor proteins, which produce mature virions. This makes the protease an attractive target for inhibitor design.
  • HTLV-I Protease and Synthesis of Inhibitors for the treatment of HTLV-I Infection 55 th Southeast Regional Meeting of the American Chemical Society, Atlanta, GA, US November 16- 19, 2003 (2003), 1073. CODEN; 69EUCH Conference, AN 2004:137641 CAPLUS Plasmepsins are essential aspartyl protease enzymes of the malarial parasite.
  • the present invention relates to compounds having the following structural formula:
  • X is -N- or -C(R 14 )-, with the proviso that when X is -N-, Y cannot be -S-;
  • Y is -N(R 5 )-, -O-, -S-, -C(R 6 )(R ea )-, -C(O)-, -S(O)- or -S(O) 2 -;
  • R 1 , R 2 and R 5 are independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalky
  • R 3 , R 4 , R 6 , R 68 and R 7 are independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alky
  • R 8 is independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl
  • R 14 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl
  • R 10 is independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl
  • R 11 , R 12 and R 13 are independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalky
  • R 15 , R 16 and R 17 are independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalky
  • R 23 numbers 0 to 5 substituents, m is 0 to 6 and n is 0 to 5;
  • R 18 is 1-5 substituents independently selected from the group consisting of alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl,
  • R 19 is alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, hetero
  • R 20 is halo substituted aryl, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylal
  • R 23 is 1 to 5 groups independently selected from the group consisting of alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl,
  • R 27 is 1-5 substituents independently selected from the group consisting of alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl,
  • R 28 is alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl,
  • R 29 is alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, aryl, cycloalkylaryl, hetero
  • the present invention provides a pharmaceutical composition comprising at least one compound of formula I and a pharmaceutically acceptable carrier.
  • the present invention provides a method of inhibiting aspartyl proteases comprising administering at least one compound of formula I to a patient in need of such treatment.
  • the present invention provides a method of inhibiting the deposition and/or accumulation of aspartyl proteases comprising administering at least one compound of formula I to a patient in need of such treatment.
  • the present invention provides a method of inhibiting the deposition and/or accumulation of A ⁇ plaque comprising administering at least one compound of formula I to a patient in need of such treatment.
  • the invention provides: a method of treating cardiovascular diseases such as hypertension, renal failure, congestive heart failure or another disease modulated by renin inhibition; a method of treating Human Immunodeficiency Virus; a method of treating cognitive or neurodegenerative diseases such as Alzheimer's Disease, glaucoma, and/or impaired olfactory function; a method of inhibiting plasmepsins I and Il for treatment of malaria; a method of inhibiting Cathepsin D for the treatment of Alzheimer's Disease, breast cancer, and/or ovarian cancer; and a method of inhibiting protozoal enzymes, for example inhibition of Plasmodium falcipamum, for the treatment of fungal infections.
  • cardiovascular diseases such as hypertension, renal failure, congestive heart failure or another disease modulated by renin inhibition
  • a method of treating Human Immunodeficiency Virus a method of treating cognitive or neurodegenerative diseases such as Alzheimer's Disease, glaucoma, and/or impaired olfactory function
  • These methods of treatment independently comprise administering at least one compound of formula I (or a stereoisomer, tautomer, or pharmaceutical salts and/or solvates thereof), to a patient in need of such treatment.
  • the invention comprises a method of treating Alzheimer's Disease comprising administering at least one compound of formula I to a patient in need of such treatment.
  • the present invention provides a method of treating Alzheimer's Disease comprising administering to a patient in need of such treatment a combination of at least one compound of formula I and a cholinesterase inhibitor or a muscarinic mi agonist or m 2 antagonist.
  • the present invention provides a method of inhibiting apoptosis of retinal ganglion cells and a method of treating or preventing glaucoma comprising administering to a patient in need of such treatment at least one compound of formula I alone or in combination with one or more additional active agents.
  • additional agents include, but are not limited to, a beta-amyloid antibody, Congo Red, and an intraocular pressure reducing agent.
  • the present invention provides a method of treating glaucoma comprising administering to a patient in need of such treatment at least one compound of formula I alone or in combination with one or more additional active agents.
  • additional agents include, but are not limited to, a beta-amyloid antibody, Congo Red, and an intraocular pressure reducing agents.
  • the present invention provides a kit comprising in separate containers in a single package pharmaceutical compositions for use in combination, in which one container comprises a compound of formula I in a pharmaceutically acceptable carrier and a second container comprises a cholinesterase inhibitor or a muscarinic mi agonist or rri 2 antagonist in a pharmaceutically acceptable carrier, the combined quantities being an effective amount to treat one or more diseases or conditions described herein, such as a cognitive disease or neurodegenerative disease such as Alzheimer's Disease.
  • the present invention relates to compounds having the structural Formula (I)
  • X is -N- or -C(R 30 )-, with the proviso that when X is -N-, Y cannot be -S-;
  • Y is -N(R 5 )-, -0-, -S-, -C(R 6 )(R 6a )-, -C(O)-, -S(O)- or -S(O) 2 -;
  • each of R 1 , R 2 and R 5 is independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cyclo
  • -NHC(O)NH 2 -NHC(O)NH(alkyl), -NHC(O)N(alkyl)(alkyl), -N(alkyl)C(O)NH(alkyl), -N(alkyl)C(O)N(alkyl)(alkyl), -NHS(O) 2 R 20 , -NHS(O) 2 NH(alkyl), -NHS(O) 2 N(alkyl)(alkyl), -N(alkyl)S(O) 2 NH(alkyl) and -N(alkyl)S(O) 2 N(alkyl)(alkyl); or two R 18 moieties on adjacent carbons can be linked together to form
  • each R 19 is independently selected from the group consisting of alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkenyl,
  • R 24 , R 25 and R 26 is independently selected from the group consisting of H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalke ⁇ yl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkenyl, arylalken
  • R 1 is alkyl. In another embodiment, R 1 is methyl.
  • R 2 is H.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkynyl, ary
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkenylaryl or heterocyclo
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula I, R 3 is heteroaryl or aryl.
  • R 3 is R W 21 S
  • R 21 is -CN.
  • the invention provides compounds of Formula I
  • R 3 is .
  • R 4 is H, alkyl or halo.
  • Z is a bond
  • R 14 is alkyl or halo. In another embodiment, in Formula I, wherein R 14 is methyl.
  • R 14 is F.
  • X is a carbon or nitrogen
  • Y is -C(R 6 )(R 6a )-.
  • R 6 is H and R 6a is H.
  • Z is a bond and Y is -C(R 6 )(R 6a )-.
  • Z is a bond; Y is -C(R 6 )(R 6a )-; and ring A together with V and X forms a moiety selected from:
  • Y is -CH 2 -.
  • each R 23 independently numbers 0 to 5 substituents, each R 23 is independently as defined above, each m is, independently, 0 to 6, each n is, independently, 0 to 5, and each q is independently 1 to 5.
  • Non-limiting examples of compounds of Formula I include the following:
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (II):
  • W is -S(O)-, -S(O) 2 -, or-O-, and R 1 , R 2 , R 3 , R 4 , Z, X, Y, V, ring A, R 14 , and p are as defined in Formula I.
  • W is -S(O)- or -S(O)2-. In another embodiment, in Formula (II), W is-O-.
  • V is a carbon atom and V, X, and ring
  • V is a carbon atom and V, X, and ring
  • V is a carbon atom and V, X, and ring
  • R 1 is alkyl. In another embodiment, in Formula (II), R 1 is methyl.
  • R 2 is H.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkynyl, ary
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkenylaryl or heterocyclo
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (II), R 3 is heteroaryl or aryl.
  • R 3 is
  • R is NC
  • R 3 is In another embodiment, in Formula (II), R 4 is H. In another embodiment, in Formula (II), R 4 is alkyl.
  • R 4 is halo
  • p is 1. In another embodiment, in Formula (II), p is 2.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (II), at least one group R 14 is alkyl. In another embodiment, in Formula (II), at least one group R 14 is arylalkyl. In another embodiment, in Formula (II), at least one group R 14 is heteroarylalkyl. In another embodiment, in Formula (II), at least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl. In another embodiment, in Formula (II), at least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl. In another embodiment, in Formula (II), at least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl. In another embodiment, in Formula (II), at least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl. In another embodiment, in Formula (II), at least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl. In another embodiment, in Formula (II), at least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl. In another embodiment, in Formula (II), at least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl. In another embodiment, in Formula (II), at least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 )(R 10 )(R 19 ). In another embodiment, in Formula (II), at least one group R 14 is
  • At least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 . In another embodiment, in Formula (II), at least one group R 14 is -C(O)OR 15 . In another embodiment, in Formula (II), at least one group R 14 is -C(O)N(R 15 )(R 16 ).
  • At least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 XR 16 ). In another embodiment, in Formula (II), at least one group R 14 : is.
  • At least one group R 14 is -N(R 15 )(R 16 ). IInn aannootthheer embodiment, in Formula (II), at least one group R 14 is -N(R 15 )C(O)R 16 . In another embodiment, in Formula (II), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O) 2 R 16 .
  • At least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III):
  • R 1 , R 2 , R 3 , R 4 , Z, Y, X, V, ring A, p, and each R 14 is selected independently of each other and wherein: ring A forms a mono or multicyclic 4 to 12 membered heteroarylene ring, and R 1 , R 2 , R 3 , R 4 , Z, X, Y, V, R 14 , and p are as defined in Formula I.
  • ring A together with V and X forms a monocyclic heteroarylene ring. In another embodiment, in Formula (III), ring A together with V and X forms a multicyclic heteroarylene ring.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 1 to 4 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 1 ring heteroatom independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 2 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 3 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • V is a carbon atom and V, X, and ring
  • V is a carbon atom and V, X, and ring
  • V is a carbon atom and V, X, and ring
  • ring A together with V and X forms a pyrazolyl, furanyl, theinyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyridonyl, imidazolyl, or pyrazinyl ring.
  • ring A together with V and X and -(R 14 )p forms a group selected from:
  • ring A together with V and X forms an 8-10-membered bicyclic heteroarylene ring having 1 or more ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a quinoxalinyl, phthalazinyl, oxindolyl, imidazopyridinyl, imidazothiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, quinazolinyl, isoquinolinyl, triazinyl, benzothiazoly, thieonpyridyl, thienopyrimidyl, imidazolpyridyl, or a pyrrolopyridyl ring.
  • R 1 is alkyl. In another embodiment, in Formula (III), R 1 is methyl.
  • R 2 is H.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkynyl, ary
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl or heterocycloal
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl.
  • R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is
  • R 3 is
  • R 3 is
  • R 3 is In another embodiment, in Formula (III), R 4 is H. In another embodiment, in Formula (III), R 4 is alkyl. In another embodiment, in Formula (III), R 4 is halo.
  • p is 0 (and R 14 is not present). In another embodiment, in Formula (III), p is 1. In another embodiment, in Formula (III), p is 2. In another embodiment, in Formula (III), p is 3. In another embodiment, in Formula (III), p is 4. In another embodiment, in Formula (III), p is 5.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H.
  • At least one group R 14 is alkyl.
  • At least one group R 14 is arylalkyl. In another embodiment, in Formula (III), at least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl. In another embodiment, in Formula (III), at least one group R 14 is aryl heterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl. In another embodiment, in Formula (III), at least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is a rylheterocycloa lkyl .
  • At least one group R 14 is heteroarylheterocycloalkyl. In another embodiment, in Formula (III), at least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl. In another embodiment, in Formula (III), at least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl. In another embodiment, in Formula (III), at least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl. In another embodiment, in Formula (III), at least one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl. In another embodiment, in Formula (III), at least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo. In another embodiment, in Formula (III), at least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (III), at least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • At least one group R 14 is -C(O)OR 15 . In another embodiment, in Formula (III), at least one group R 14 is -C(O)N(R 15 )(R 16 ). In another embodiment, in Formula (III), at least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 XR 16 ).
  • At least one group R 14 is -S(O) 2 N(R 15 XR 16 ). In another embodiment, in Formula (III), at least one group R 14 is
  • At least one group R 14 is -P(O)(OR 15 XOR 16 ).
  • At least one group R 14 is -N(R 15 )(R 16 ). In another embodiment, in Formula (III), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O)R 16 .
  • At least one group R 14 is -N(R 15 JS(O) 2 R 16 .
  • At least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ). In another embodiment, in Formula (III), at least one group R 14 is
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III. a.):
  • R 1 , R 2 , R 3 , R 4 , Y, X, V, ring A, p, and each R 14 is selected independently of each other and wherein: ring A forms a mono or multicyclic 4 to 12 membered heteroarylene ring, and R 1 , R 2 , R 3 , R 4 , X, Y, V, A 1 R 14 , and p are as defined in Formula I.
  • ring A together with V and X forms a monocyclic 4 to 12 membered heteroarylene.
  • ring A together with V and X forms a monocyclic heteroarylene ring.
  • ring A together with V and X forms a multicyclic heteroarylene ring.
  • ring A together with V and X forms a bicyclic heteroarylene ring.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 1 to 4 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 1 ring heteroatom independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 2 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 3 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • V is a carbon atom and V, X, and
  • V is a carbon atom and V, X, and
  • V is a carbon atom and V, X, and
  • -V-X- is S X NV f .
  • ring A together with V and X forms a pyrazolyl, furanyl, theinyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyridonyl, imidazolyl, or pyrazinyl ring.
  • ring A and -(R 14 ) p is selected from the group consisting of:
  • ring A together with V and X forms an 8-10-membered bicyclic heteroarylene ring having 1 or more ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a quinoxalinyl, phthalazinyl, oxindolyl, imidazopyridinyl, imidazothiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, quinazolinyl, isoquinolinyl, triazinyl, benzothiazoly, thieonpyridyl, thienopyrimidyl, imidazolpyridyl, or a pyrrolopyridyl ring.
  • R 1 is alkyl. In another embodiment, in Formula (III. a.), R 1 is methyl.
  • R 2 is H.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkenylaryl or
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl.
  • R 3 is heteroaryl or aryl.
  • R ⁇ 3 is
  • R is R 21
  • R 3 is .
  • R 4 is H.
  • R 4 is alkyl
  • R 4 is halo
  • p is 3. In another embodiment, in Formula (lll.a.), p is 4.
  • p is 5. In another embodiment, in Formula (III. a.), p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula .a.), at least one group R 14 is alkyl.
  • At least one group R 14 i.s arylalkyl
  • At least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl. In another embodiment, in Formula .a.), at least one group R 14 is heteroarylcycloalkylalkyl. IInn aannootthheerr eemmbbooddiiment, in Formula (III. a.), at least one group R 14 is arylheterocycloalkylalkyl. IInn aannootthheerr eemmbbooddiiment, in Formula (III. a.), at least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl In another embodiment, in Formula .a.), at least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • IInn aannootthheerr eermr bodiment in Formula (lll.a.), at least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl. In another embodiment, in Formula (lll.a.), at least one group R 14 is arylalkenyl. In another embodiment, in Formula (III. a.), at least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl. In another embodiment, in Formula (III. a.), at least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl. In another embodiment, in Formula (lll.a.), at least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl. In another embodiment, in Formula (lll.a.), at least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is heteroaryl. In another embodiment, in Formula (lll.a.), at least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo. In another embodiment, in Formula (lll.a.), at least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.a.), at least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 1
  • At least one group R 14 is - C(O)OR 15 . In another embodiment, in Formula (lll.a.), at least one group R 14 is
  • At least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 KR 16 ). In another embodiment, in Formula (lll.a.), at least one group R 14 is
  • At least one group R 14 is -P(O)(OR 15 KOR 16 ).
  • At least one group R 14 is - N(R 15 KR 16 ).
  • At least one group R 14 is -N(R 15 )C(O)R 16 . In another embodiment, in Formula (lll.a.), at least one group R 14 is
  • At least one group R 14 is -N(R 15 JS(O) 2 R 16 .
  • At least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is
  • At least one group R 1 1"4 i s. -N(R 15 )C(O)N(R 16 )(R 17 ).
  • at least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c):
  • R 1 , R 2 , R 3 , R 4 , R 6 , R 6a , X, V, ring A, p, and each R 14 is selected independently of each other and wherein: ring A forms a mono or multicyclic 4 to 12 membered heteroarylene ring, and R 1 , R 2 , R 3 , R 4 , R 6 , R 6a , X, V 1 A, R 14 , and p are as defined in Formula I.
  • ring A together with V and X forms a monocyclic 4 to 12 membered heteroarylene.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 1 to 4 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 1 ring heteroatom independently selected from the group consisting of N, O 1 and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 2 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • ring A together with V and X forms a 5-6-membered monocyclic heteroarylene ring having from 3 ring heteroatoms independently selected from the group consisting of N, O, and S.
  • V is a carbon atom and V, X, and
  • V is a carbon atom and V, X, and
  • V is a carbon atom and V, X, and
  • ring A together with V and X forms a pyrazolyl, furanyl, theinyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, pyrazolyl, furazanyl, pyrrolyl, pyrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyridonyl, imidazolyl, or pyrazinyl ring.
  • ring A and -(R 14 ) p is selected from the group consisting of:
  • ring A together with V and X forms a quinoxalinyl, phthalazinyl, oxindolyl, imidazopyridinyl, imidazothiazolyl, benzofurazanyl, indolyl, azaindolyl, benzimidazolyl, benzothienyl, quinolinyl, quinazolinyl, isoquinolinyl, triazinyl, benzothiazoly, thieonpyridyl, thienopyrimidyl, imidazolpyridyl, or a pyrrolopyridyl ring.
  • R 1 is alkyl. In another embodiment, in Formula (lll.c), R 1 is methyl.
  • R 2 is H.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkynyl,
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl or hetero
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl.
  • R 3 is heteroaryl or aryl.
  • R 3 is
  • R is R 21
  • R is
  • R 3 is In another embodiment, in Formula (lll.c), R 4 is H. In another embodiment, in Formula (lll.c), R 4 is alkyl.
  • R 4 is halo
  • R 6 is H. In another embodiment, in Formula (lll.c), R 6 is alkyl. In another embodiment, in Formula (lll.c), R 6 is methyl
  • R 6 is ethyl.
  • R ⁇ 3a is H -
  • R 6a is alkyl. In another embodiment, in Formula (lll.c), R 6a is methy In another embodiment, in Formula (lll.c), R 6a is ethyl.
  • p is 2. In another embodiment, in Formula (lll.c), p is 3.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H.
  • At least one group R 14 is alkyl.
  • At least one group R 14 is arylalkyl.
  • At least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • IInn aannootthher embodiment in Formula (lll.c), at least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl. In another embodiment, in Formula (lll.c). at least one group R 14 is arylcycloalkyl.
  • At ' east one group R 14 is heteroarylcycloalkyl. In another embodiment, in Formula (lll.c), at least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl. In another embodiment, in Formula (lll.c), at least one group R 14 is arylcycloalkenyl. IInn aannootthheer embodiment, in Formula (lll.c), at least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl. IInn aannootthheerr eemmbbcodiment, in Formula (lll.c), at least one group R 14 is heteroarylheterocycloalkenyl. In another embodiment, in Formula (lll.c), at least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl. In another embodiment, in Formula (lll.c), at least one group R 14 is aryl. In another embodiment, in Formula (lll.c), at least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl. In another embodiment, in Formula (lll.c), at least one group R 14 is heterocycloalkenylaryl.
  • At 'east one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl. In another embodiment, in Formula (lll.c), at least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo.
  • At least one group R 14 is IInn aannootthheerr eemmbbooddiment
  • at least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -CN. In another embodiment, in Formula (lll.c), at least one group R 14 is -OR 15 . In another embodiment, in Formula (lll.c), at least one group R 14 is -C(O)R 15 . In another embodiment, in Formula (lll.c), at least one group R 14 is
  • At least one group R 14 is -C(O)N(R 15 XR 16 ).
  • At least one group R 14 is -SR 15 . In another embodiment, in Formula (lll.c), at least one group R 14 is
  • At least one group R 14 is
  • At least one group R 14 ⁇ is
  • At least one group R 14 is -
  • at least one group R 14 is -N(R 15 )C(O)R 16 .
  • At 'east one group R 14 is -N(R 15 )S(O)R 16 .
  • At least one group R 14 is -N(R 15 )S(O) 2 R 16 .
  • At least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.1 ):
  • R 1 is alkyl
  • R 1 is methyl
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (lll.c.1), R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is R W 21 S
  • R 3 is .
  • p is 0 (and R 14 is not present). In another embodiment, in Formula (lll.c.1 ), p is 1. In another embodiment, in Formula (lll.c.1 ), p is 2.
  • p is 3. In another embodiment, in Formula (lll.c.1), p is 4.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H.
  • At least one group R 14 is alkyl.
  • At least one group R 14 is arylalkyl.
  • At least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl. In another embodiment, in Formula (lll.c.1), at least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl. In another embodiment, in Formula (lll.c.1), at least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl. In another embodiment, in Formula (lll.c.1 ), at least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl. In another embodiment, in Formula (lll.c.1 ), at least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is heteroaryl. In another embodiment, in Formula (lll.c.1), at least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl. In another embodiment, in Formula (lll.c.1), at least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl. In another embodiment, in Formula (lll.c.1 ), at least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.1 ), at least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • At least one group R 14 is - C(O)OR 15 . In another embodiment, in Formula (lll.c.1), at least one group R 14 is
  • At least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 XR 16 ). In another embodiment, in Formula (lll.c.1), at least one group R 14 is
  • At least one group R 14 is -P(O)(OR 15 XOR 16 ).
  • At least one group R 14 is - N(R 15 XR 16 ).
  • At least one group R 14 is -N(R 15 )C(O)R 16 . In another embodiment, in Formula (lll.c.1), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O) 2 R 16 . In another embodiment, in Formula (lll.c.1 ), at least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.1 ), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.1 A):
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.2):
  • R 1 is alkyl
  • R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, heteroarylheterocycloalkyl, alkenyl,
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl.
  • R 3 is heteroaryl or aryl.
  • R 3 is
  • R is
  • R 3 In another embodiment, in Formula (lll.c.2), p is 0 (and R 14 is not present). In another embodiment, in Formula (lll.c.2), p is 1. In another embodiment, in Formula (lll.c.2), p is 2. In another embodiment, in Formula (lll.c.2), p is 3. In another embodiment, in Formula (lll.c.2), p is 4. In another embodiment, in Formula (lll.c.2), p is 5.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (lll.c.2), at least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is arylalkyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is cycloalkenylaryl. IInn aannootthheer embodiment, in Formula (lll.c.2), at least one group R 14 is heterocycloalkenylaryl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl. In another embodiment, in Formula (lll.c.2), at least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 XR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • At least one group R 14 is - C(O)OR 15 .
  • At least one group R 14 is -C(O)N(R 15 XR 16 ).
  • At least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 XR 16 ).
  • At least one group R 14 is -S(O) 2 N(R 15 XR 16 ).
  • At least one group R 14 is - N(R 15 XR 16 ). In another embodiment, in Formula (lll.c.2), at least one group R 14 is -N(R 15 )C(O)R 16 .
  • At least one group R 14 is -N(R 15 )S(O)R 16 . In another embodiment, in Formula (lll.c.2), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 JC(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III. c.2A):
  • p is 0-3 and R 1 , R 3 , R 14 are as defined in Formula (lll.c.2).
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.2B1):
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.3):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-3 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl
  • R 1 is methyl
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (lll.c.3), R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is R 21
  • R is NC
  • R is
  • p is 1. In another embodiment, in Formula (lll.c.3), p is 2.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (lll.c.3), at least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is arylalkyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is heteroarylalkyl.
  • At least one group R is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is heterocycloalkyl. IInn aannootthheeir embodiment, in Formula (lll.c.3), at least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenyl heteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl. In another embodiment, in Formula (lll.c.3), at least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 XR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.3), at least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • at least one group R 14 is - C(O)OR 15 .
  • at least one group R 14 is -C(O)N(R 15 KR 16 ).
  • At least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 KR 16 ).
  • At least one group R 14 is -S(O) 2 N(R 15 KR 16 ).
  • At least one group R 14 is - N(R 15 KR 16 ).
  • At least one group R 14 is -N(R 15 )C(O)R 16 .
  • At least one group R 14 is -N(R 15 )S(O)R 16 .
  • At least one group R 14 is -N(R 15 )S(O) 2 R 16 . In another embodiment, in Formula (lll.c.3), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.3A): (III.C.3A) wherein R 1 , R 14 , and R 21 are selected independently and R 1 and R 14 are as defined in Formula (lll.c.3) and R 21 is as defined in Formula (I).
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.4):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-3 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl. In another embodiment, in Formula (lll.c.4), R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl.
  • R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is
  • R 3 is NC W S
  • R 3 is .
  • p is 1. In another embodiment, in Formula (lll.c.4), p is 2.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • at least one group R 14 is H.
  • At least one group R 14 is alkyl.
  • At least one group R 14 is arylalkyl.
  • At least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl. In another embodiment, in Formula (lll.c.4), at least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl. In another embodiment, in Formula (lll.c.4), at least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl. In another embodiment, in Formula (lll.c.4), at least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • at least one group R 14 is cycloalkenyl.
  • at least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl. In another embodiment, in Formula (lll.c.4), at least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl. In another embodiment, in Formula (lll.c.4), at least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo. In another embodiment, in Formula (lll.c.4), at least one group R 14 is -CH 2 -O-Si(R 9 XR 10 XR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • At least one group R 14 is -
  • At least one group R 14 is -SR 15 . In another embodiment, in Formula (lll.c.4), at least one group R 14 is -S(O)N(R 15 XR 16 ). In another embodiment, in Formula (lll.c.4), at least one group R 14 is
  • At least one group R 14 is -P(O)(OR 15 XOR 16 ).
  • At least one group R 14 is - N(R 15 XR 16 ).
  • At least one group R 14 is -N(R 15 )C(O)R 16 . In another embodiment, in Formula (lll.c.4), at least one group R 14 is
  • At least one group R 14 is
  • At least one group R 14 in Formula (lll.c.4), at least one group R 14 : i.s -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.4), at least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III. c.4A):
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.5):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-2 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl. In another embodiment, in Formula (lll.c.5), R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (lll.c.5), R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is
  • R 3 is N WC S
  • R is
  • p is 0 (and R 14 is not present). In another embodiment, in Formula (lll.c.5), p is 1. In another embodiment, in Formula (lll.c.5), p is 2. In another embodiment, in Formula (lll.c.5), p is 3.
  • p is 4. In another embodiment, in Formula (lll.c.5), p is 5.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (lll.c.5), at least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is arylalkyl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is heteroarylalkyl. IInn aannootthher embodiment, in Formula (lll.c.5), at least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is arylheterocycloalkyl. IInn aannootthheerr eermr bodiment, in Formula (lll.c.5), at least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl.
  • IInn aannootthheerr eemi bodiment in Formula (lll.c.5), at least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl. In another embodiment, in Formula (lll.c.5), at least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • IInn aannootthheerr eermr bodiment in Formula (lll.c.5), at least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloa lkenylheteroa ryl . In another embodiment, in Formula (lll.c.5), at least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 in Formula (lll.c.5). In another embodiment, in Formula (lll.c.5), at least one group R 14 is -C(O)R 15 .
  • At least one group R 14 is - C(O)OR 15 .
  • At least one group R 14 is -C(O)N(R 15 XR 16 ). In another embodiment, in Formula (lll.c.5), at least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 XR 16 ).
  • At least one group R 14 is -P(O)(OR 15 XOR 16 ).
  • At least one group R 14 is - N(R 15 XR 16 ).
  • At least one group R 14 is -N(R 15 )C(O)R 16 .
  • At least one group R 14 is -N(R 15 )S(O)R 16 . In another embodiment, in Formula (lll.c.5), at least one group R 14 is
  • At least one group R i14 i s, -N(R 15 )S(O) 2 N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.5), at least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.5), at least one group R 14 is
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.5A):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-2 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl. In another embodiment, in Formula (lll.c.6), R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (lll.c.6), R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is
  • R 3 is NC W S
  • R 3 is
  • p is 1. In another embodiment, in Formula (lll.c.6), p is 2. In another embodiment, in Formula (lll.c.6), p is 3. In another embodiment, in Formula (lll.c.6), p is 4. In another embodiment, in Formula (lll.c.6), p is 5. In another embodiment, in Formula (lll.c.6), p is 2-5 and at least two groups
  • R 14 are bound to the same ring atom.
  • At least one group R 14 is H.
  • At least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is arylalkyl.
  • At least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is cycloalkylheteroaryl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl. In another embodiment, in Formula (lll.c.6), at least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ). In another embodiment, in Formula (lll.c.6), at least one group R 14 is
  • At least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 . In another embodiment, in Formula (lll.c.6), at least one group R 14 is -
  • At least one group R 14 is -C(O)N(R 15 XR 16 ).
  • At least one group R 14 is -SR 15 . In another embodiment, in Formula (lll.c.6), at least one group R 14 is
  • At least one group R 14 is -S(O) 2 N(R 15 XR 16 ).
  • At least one group R 14 is -P(O)(OR 15 XOR 16 ).
  • At least one group R 14 is -
  • At least one group R 14 is -N(R 15 JS(O)R 16 . In another embodiment, in Formula (lll.c.6), at least one group R 14 is
  • At least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.6A):
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.7):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-2 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl. In another embodiment, in Formula (lll.c.7), R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (lll.c.7), R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is NC W S In another embodiment, in Formula (lll.c.7), R 3 is
  • p is 0 (and R 14 is not present). In another embodiment, in Formula (lll.c.7), p is 1. In another embodiment, in Formula (lll.c.7), p is 2.
  • p is 3. In another embodiment, in Formula (lll.c.7), p is 4. In another embodiment, in Formula (lll.c.7), p is 5.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (lll.c.7), at least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is arylalkyl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloa lkyla ryl . In another embodiment, in Formula (lll.c.7), at least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl. In another embodiment, in Formula (lll.c.7), at least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.7), at least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • at least one group R 14 is - C(O)OR 15 .
  • at least one group R 14 is
  • At least one group R 14 is -SR 15 . In another embodiment, in Formula (lll.c.7), at least one group R 14 is -S(O)N(R 15 XR 16 ). In another embodiment, in Formula (lll.c.7), at least one group R 14 is
  • At least one group R 14 is -
  • At least one group R 14 is -N(R 15 JS(O) 2 R 16 .
  • At least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.7), at least one group R 14 is
  • At least one group R 14 is -N(R 15 JC(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.7A):
  • R 1 , R 14 , and R 21 are selected independently and R 1 and R 14 are as defined in Formula (lll.c.7) and R 21 is as defined in Formula (I).
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.8):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-2 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl. In another embodiment, in Formula (lll.c.8), R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl, heteroaryl, cycloalkylheter
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (lll.c.8), R 3 is heteroaryl or aryl.
  • R 3 is
  • R 3 is R 21
  • R 3 is NC W S
  • R 3 is .
  • p is 1. In another embodiment, in Formula (lll.c.8), p is 2.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (lll.c.8), at least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is arylalkyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • IInn aannootthheerr eemrr bodiment in Formula (lll.c.8), at least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl.
  • At least one group R 14 is heteroarylcycloalkenyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is heterocycloalkenyl.
  • At least one group R 14 is arylheterocycloalkenyl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl.
  • At least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl.
  • At least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is heteroaryl.
  • At least one group R 14 is cycloalkylheteroaryl.
  • IInn aannootthheerr eermr bodiment in Formula (lll.c.8), at least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl. In another embodiment, in Formula (lll.c.8), at least one group R 14 is halo.
  • At least one group R 14 is -CH 2 -O-Si(R 9 XR 10 KR 19 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ). In another embodiment, in Formula (lll.c.8), at least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 .
  • At least one group R 14 is -C(O)R 15 .
  • at least one group R 14 is - C(O)OR 15 .
  • at least one group R 14 is -C(O)N(R 15 XR 16 ).
  • At least one group R 14 is -SR 15 . In another embodiment, in Formula (lll.c.8), at least one group R 14 is -S(O)N(R 15 XR 16 ).
  • At least one group R 14 is - N(R 15 XR 16 ).
  • At least one group R 14 is -N(R 15 )C(O)R 16 .
  • At least one group R is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.8A):
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (lll.c.9):
  • R 1 , R 3 , R 14 , and p are selected independently, and wherein p is 0-2 and R 1 , R 3 , R 14 are as defined in Formula (I).
  • R 1 is alkyl. In another embodiment, in Formula (lll.c.9), R 1 is methyl.
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkyny
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalke ⁇ ylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenyla
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl.
  • R 3 is heteroaryl or aryl.
  • R - is
  • R 3 is .
  • p is 3. In another embodiment, in Formula (lll.c.9), p is 4.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H.
  • At least one group R 14 is alkyl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is arylalkyl.
  • At least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl.
  • At least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl.
  • At least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.
  • At least one group R 14 is heteroarylheterocycloalkyl.
  • At least one group R 14 is alkenyl.
  • At least one group R 14 is arylalkenyl.
  • At least one group R 14 is cycloalkenyl.
  • At least one group R 14 is arylcycloalkenyl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is heteroarylcycloalkenyl.
  • At least one group R 14 is heterocycloalkenyl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is arylheterocycloalkenyl.
  • At least one group R 14 is heteroarylheterocycloalkenyl.
  • At least one group R 14 is alkynyl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is arylalkynyl.
  • At least one group R 14 is aryl.
  • At least one group R 14 is cycloalkylaryl. In another embodiment, in Formula (lll.c.9), at least one group R 14 is heterocycloalkylaryl.
  • At least one group R 14 is cycloalkenylaryl.
  • At least one group R 14 is heterocycloalkenylaryl.
  • At least one group R 14 is heteroaryl.
  • at least one group R 14 is cycloalkylheteroaryl.
  • at least one group R 14 is heterocycloalkylheteroaryl.
  • At least one group R 14 is cycloalkenylheteroaryl.
  • At least one group R 14 is heterocycloalkenylheteroaryl.
  • At least one group R 14 is halo. In another embodiment, in Formula (lll.c.9), at least one group R 14 is -CH 2 -O-Si(R 9 XR 10 XR 19 ). In another embodiment, in Formula (lll.c.9), at least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -CN.
  • At least one group R 14 is -OR 15 in Formula (lll.c.9). In another embodiment, in Formula (lll.c.9), at least one group R 14 is -C(O)R 15 .
  • At least one group R 14 is - C(O)OR 15 .
  • At least one group R 14 is -C(O)N(R 15 XR 16 ). In another embodiment, in Formula (lll.c.9), at least one group R 14 is -SR 15 .
  • At least one group R 14 is -S(O)N(R 15 XR 16 ).
  • At least one group R 14 is
  • At least one group R 14 is
  • At least one group R 14 is -
  • At least one group R 14 is -N(R 15 )C(O)R 16 .
  • At least one group R 14 is -N(R 15 )S(O)R 16 . In another embodiment, in Formula (lll.c.9), at least one group R 14 is
  • At least one group R 14 is -N(R 15 )S(O) 2 N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )S(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)N(R 16 )(R 17 ).
  • At least one group R 14 is -N(R 15 )C(O)OR 16 .
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (III.C.9A):
  • the present invention provides a compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, having the general structure shown in Formula (IV):
  • R 1 , R 2 , R 3 , R 4 , Z, Y, X, V, ring A, p, and each R 14 is selected independently of each other and wherein: ring A forms a mono or multicyclic 4 to 12 membered arylene ring, and R 1 , R 2 , R 3 , R 4 , Z 1 X, Y, V, R 14 , and p are as defined in Formula I.
  • V is a carbon atom and V, X, and ring
  • V is a carbon atom and V, X, and ring
  • R 1 is alkyl. In another embodiment, in Formula (IV), R 1 is methyl.
  • R is H
  • R 3 is H, alkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, cycloalkyl, arylcycloalkyl, heteroarylcycloalkyl, heterocycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, alkenyl, arylalkenyl, cycloalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, heterocycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, alkynyl, arylalkynyl, arylalkynyl, ary
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkylalkyl, heteroarylcycloalkylalkyl, arylheterocycloalkylalkyl, heteroarylheterocycloalkylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, heteroarylheterocycloalkyl, arylalkenyl, arylcycloalkenyl, heteroarylcycloalkenyl, arylheterocycloalkenyl, heteroarylheterocycloalkenyl, arylalkynyl, aryl, cycloalkylaryl, heterocycloalkylaryl, heterocycloalkenylaryl, heteroaryl, cycloalkylheteroaryl, heterocycloalkylheteroaryl, cycloalkenylaryl or heterocycloal
  • R 3 is arylalkyl, heteroarylalkyl, arylcycloalkyl, heteroarylcycloalkyl, arylalkenyl, arylalkynyl, aryl or heteroaryl. In another embodiment, in Formula (IV), R 3 is heteroaryl or aryl.
  • R 3 is
  • R a is NC W s
  • R 3 is .
  • R 4 is H. In another embodiment, in Formula (IV), R 4 is alkyl. In another embodiment, in Formula (IV), R 4 is halo.
  • p is 4. In another embodiment, in Formula (IV), p is 5.
  • p is 2-5 and at least two groups R 14 are bound to the same ring atom.
  • At least one group R 14 is H. In another embodiment, in Formula (IV), at least one group R 14 is alkyl.
  • At least one group R 14 is arylalkyl. In another embodiment, in Formula (IV), at least one group R 14 is heteroarylalkyl.
  • At least one group R 14 is cycloalkylalkyl. In another embodiment, in Formula (IV), at least one group R 14 is heterocycloalkylalkyl.
  • At least one group R 14 is arylcycloalkylalkyl.
  • At least one group R 14 is heteroarylcycloalkylalkyl.
  • At least one group R 14 is arylheterocycloalkylalkyl.
  • At least one group R 14 is heteroarylheterocycloalkylalkyl. In another embodiment, in Formula (IV), at least one group R 14 is cycloalkyl.
  • At least one group R 14 is arylcycloalkyl.
  • At least one group R 14 is heteroarylcycloalkyl.
  • At least one group R 14 is heterocycloalkyl.
  • At least one group R 14 is arylheterocycloalkyl.

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Abstract

L'invention concerne des composés représentés par la formule I (la formule chimique doit être insérée ici comme elle apparaît dans l'abrégé sous forme papier) Formule I ou un stéréoisomère, un tautomère, ou un sel ou un solvate pharmaceutiquement acceptable de ceux-ci, dans laquelle R1, R2, R3, R4, R14, V, W, X, Y, Z, p, et le cycle A sont tels que décrits dans la description. L'invention concerne également un procédé destiné à inhiber la protéase d'aspartyle et, en particulier, les procédés destinés à traiter des maladies cardio-vasculaires et des maladies cognitives et neurodégénératives. L'invention concerne également des procédés destinés à traiter des maladies cognitives ou neurodégénératives utilisant les composés représentés par la formule I en combinaison avec un inhibiteur de la cholinestérase, un agoniste muscarinique m1 ou un antagoniste m2.
PCT/US2007/025220 2006-12-12 2007-12-10 Inhibiteurs de la protéase d'aspartyle Ceased WO2008073365A1 (fr)

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MX2009006228A MX2009006228A (es) 2006-12-12 2007-12-10 Inhibidores de aspartil proteasa.
AU2007332754A AU2007332754A1 (en) 2006-12-12 2007-12-10 Aspartyl protease inhibitors
CA002672293A CA2672293A1 (fr) 2006-12-12 2007-12-10 Inhibiteurs de la protease d'aspartyle
JP2009541321A JP2010512389A (ja) 2006-12-12 2007-12-10 アスパルチルプロテアーゼ阻害剤
EP07862708.0A EP2064191B1 (fr) 2006-12-12 2007-12-10 Inhibiteurs de la protéase d'aspartyle
US12/517,744 US8093254B2 (en) 2006-12-12 2007-12-10 Aspartyl protease inhibitors

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